<i>N</i>‐Terminal Selective C−H Azidation of Proline‐Containing Peptides: a Platform for Late‐Stage Diversification

Allouche, Emmanuelle M. D.; Simonet‐Davin, Raphaël; Waser, Jérôme

doi:10.1002/chem.202200368

Cited by 10 publications

(6 citation statements)

References 54 publications

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“…41 Our group reported in 2022 also an unprecedented in situ generation of ABX (3) directly from 2-iodobenzoic acid for the C-H azidation of peptides 41 (Equation 11). 42 This protocol demonstrated an excellent regioselectivity toward the -position of N-terminus prolines protected with a carbamate to give 42. It could be applied to peptides up to seven amino acids long.…”

Section: Scheme 2 Selective Azidation or Chlorination Of A Dipeptide ...mentioning

confidence: 97%

Azidation with Hypervalent Iodine Reagents

Simonet‐Davin

Waser

2022

Synthesis

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In this short review, we describe applications of hypervalent iodine reagents for the azidation of organic compounds from the seminal publications to the most recent reports. After reviewing selected examples of azidations based on the use of in situ formed unstable non-cyclic reagents, we focus more in details on stable cyclic hypervalent iodine reagents. Important advances in the azidation of C–H bonds, alkenes as well as other transformations are described. Rather than being comprehensive, we selected to highlight the key reports that especially contributed to the advancement of research in the field in our opinion. Table of content: 1. Introduction 2. Non-Cyclic λ3-Iodanes 3. Heterocyclic λ3-Iodanes 3.1 Azidation of aliphatic C–H Bonds 3.2 Azidation of Alkenes 3.3 Other Azidations 4. Conclusion and Outlook

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Section: Scheme 2 Selective Azidation or Chlorination Of A Dipeptide ...mentioning

confidence: 97%

Azidation with Hypervalent Iodine Reagents

Simonet‐Davin

Waser

2022

Synthesis

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“…Substitution on the ring is known to impose steric and steric-electronic effects which can modulate the equilibria of both cis/trans isomerization and endo/ exo conformations as well as the rotational barriers for cis/trans isomerization (15)(16)(17)(18)(19). As a result, many efforts have been made for the late-stage editing of proline residue (20)(21)(22)(23). In particular, the C5 position of proline is of immediate impact in biological activity, for instance, cyclization of the side chains with the C5 position in the endogenous antagonist Smac to constrain the conformation lastly produced xevinapant which was acquired by Merck in 2021 (Fig.…”

Section: Introductionmentioning

confidence: 99%

Copper catalyzed Shono-type oxidation of proline residues in peptide

Chang,

Wang,

Huang

et al. 2023

Sci. Adv.

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Since the initial report in 1975, the Shono oxidation has become a powerful tool to functionalize the α position of amines, including proline derivatives, by electrochemical oxidation. However, the application of electrochemical Shono oxidations is restricted to the preparation of simple building blocks and homogeneous Shono-type oxidation of proline derivatives remains challenging. The late-stage functionalization at proline residues embedded within peptides is highly important as substitutions about the proline ring are known to affect biological and pharmacological activities. Here, we show that homogenous copper-catalyzed oxidation conditions complement the Shono oxidation and this general protocol can be applied to a series of formal C-C coupling reactions with a variety of nucleophiles using a one-pot procedure. This protocol shows good tolerance toward 19 proteinogenic amino acids and was used to functionalize several representative bioactive peptides, including captopril, enalapril, Smac, and endomorphin-2. Last, peptide cyclization can also be achieved by using an appropriately positioned side-chain hydroxyl moiety.

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“…We started our investigation using N -Boc hydroxyglycine 1a , trifluoroacetic anhydride (TFAA) as the activating reagent, triethylamine as the base and TMSN 3 or MeOH as the nucleophile. The choice of TMSN 3 was motivated by the fact that N- azide aminals are also good imine surrogates . The starting materials are easily obtained in a few steps starting from commercially available ethyl glyoxylate and hydroxylamine (see Supporting Information (SI) for details).…”

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Interrupted Polonovski Strategy for the Synthesis of Functionalized Amino Acids and Peptides

Marty,

Allouche,

Waser

2024

Org. Lett.

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The α-functionalization of carbamate-protected hydroxylamine glycine derivatives, acting as imine surrogates via an interrupted Polonovski reaction, is described to access functionalized amino acid derivatives. The addition of C, N, O, and S nucleophiles was achieved in a one-pot procedure in 37% to 92% yield. This method could be extended to dipeptide derivatives for the functionalization of both the C-terminus and N-terminus.

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N‐Terminal Selective C−H Azidation of Proline‐Containing Peptides: a Platform for Late‐Stage Diversification

Cited by 10 publications

References 54 publications

Azidation with Hypervalent Iodine Reagents

Azidation with Hypervalent Iodine Reagents

Copper catalyzed Shono-type oxidation of proline residues in peptide

Interrupted Polonovski Strategy for the Synthesis of Functionalized Amino Acids and Peptides

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